A historical perspective on ACE2 in the COVID-19 era

doi:10.1038/s41371-020-00459-3

Review

. 2021 Oct;35(10):935-939.

doi: 10.1038/s41371-020-00459-3. Epub 2020 Dec 14.

A historical perspective on ACE2 in the COVID-19 era

Vivek Bhalla^{1

2

3}, Catherine A Blish^{4

5

6}, Andrew M South^{7

8

9}

Affiliations

¹ Stanford Hypertension Center, Stanford University School of Medicine, Stanford, CA, USA. vbhalla@stanford.edu.
² Division of Nephrology, Stanford University School of Medicine, Stanford, CA, USA. vbhalla@stanford.edu.
³ Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA. vbhalla@stanford.edu.
⁴ Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
⁵ Division of Infectious Diseases and Geographical Medicine, Stanford University School of Medicine, Stanford, CA, USA.
⁶ Chan Zuckerberg Biohub, San Francisco, CA, USA.
⁷ Section of Nephrology, Department of Pediatrics, Brenner Children's Hospital, Wake Forest School of Medicine, Winston Salem, NC, USA.
⁸ Department of Surgery-Hypertension and Vascular Research, Wake Forest School of Medicine, Winston Salem, NC, USA.
⁹ Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest School of Medicine, Winston Salem, NC, USA.

PMID: 33318644
PMCID: PMC7735396
DOI: 10.1038/s41371-020-00459-3

Review

A historical perspective on ACE2 in the COVID-19 era

Vivek Bhalla et al. J Hum Hypertens. 2021 Oct.

. 2021 Oct;35(10):935-939.

doi: 10.1038/s41371-020-00459-3. Epub 2020 Dec 14.

Authors

Vivek Bhalla^{1

2

3}, Catherine A Blish^{4

5

6}, Andrew M South^{7

8

9}

Affiliations

¹ Stanford Hypertension Center, Stanford University School of Medicine, Stanford, CA, USA. vbhalla@stanford.edu.
² Division of Nephrology, Stanford University School of Medicine, Stanford, CA, USA. vbhalla@stanford.edu.
³ Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA. vbhalla@stanford.edu.
⁴ Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
⁵ Division of Infectious Diseases and Geographical Medicine, Stanford University School of Medicine, Stanford, CA, USA.
⁶ Chan Zuckerberg Biohub, San Francisco, CA, USA.
⁷ Section of Nephrology, Department of Pediatrics, Brenner Children's Hospital, Wake Forest School of Medicine, Winston Salem, NC, USA.
⁸ Department of Surgery-Hypertension and Vascular Research, Wake Forest School of Medicine, Winston Salem, NC, USA.
⁹ Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest School of Medicine, Winston Salem, NC, USA.

PMID: 33318644
PMCID: PMC7735396
DOI: 10.1038/s41371-020-00459-3

No abstract available

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

**Fig. 1. Historical context of the renin-angiotensin-aldosterone system and coronavirus.**
A Role of counter-regulatory effects of the ACE2—Ang-(1–7) pathway (blue) in the context of pathologic effects of the ACE—Ang II pathway (red). ACE2 is the receptor for SARS-CoV and SARS-CoV-2, which may decrease ACE2 cell surface expression after binding. B Timeline of discoveries of the RAAS. C Annual PubMed® citations for the two RAAS pathways and SARS (source: https://esperr.github.io/pubmed-by-year/). Ang angiotensin, Aldo Aldosterone, ACE angiotensin-converting enzyme, ACE2 angiotensin-converting enzyme 2, NEP neprilysin, AT₁R angiotensin II type 1 receptor, AT₂R angiotensin II type 2 receptor, MasR Mas receptor, SARS severe acute respiratory distress syndrome, CoV coronavirus.

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References

1. Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med. 2005;11:875–9. doi: 10.1038/nm1267. - DOI - PMC - PubMed
1. Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367(6483):1260–3. - PMC - PubMed
1. El Bekay R, Alvarez M, Monteseirin J, Alba G, Chacon P, Vega A, et al. Oxidative stress is a critical mediator of the angiotensin II signal in human neutrophils: involvement of mitogen-activated protein kinase, calcineurin, and the transcription factor NF-kappaB. Blood. 2003;102:662–71.. doi: 10.1182/blood-2002-09-2785. - DOI - PubMed
1. Garrido AM, Griendling KK. NADPH oxidases and angiotensin II receptor signaling. Mol Cell Endocrinol. 2009;302:148–58.. doi: 10.1016/j.mce.2008.11.003. - DOI - PMC - PubMed
1. Silva-Filho JL, Souza MC, Henriques M, Morrot A, Savino W, Nunes MP, et al. AT1 receptor-mediated angiotensin II activation and chemotaxis of T lymphocytes. Mol Immunol. 2011;48:1835–43.. doi: 10.1016/j.molimm.2011.05.008. - DOI - PubMed

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[1] Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med. 2005;11:875–9. doi: 10.1038/nm1267. - DOI - PMC - PubMed

[2] Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med. 2005;11:875–9. doi: 10.1038/nm1267. - DOI - PMC - PubMed

[3] Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367(6483):1260–3. - PMC - PubMed

[4] Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367(6483):1260–3. - PMC - PubMed

[5] El Bekay R, Alvarez M, Monteseirin J, Alba G, Chacon P, Vega A, et al. Oxidative stress is a critical mediator of the angiotensin II signal in human neutrophils: involvement of mitogen-activated protein kinase, calcineurin, and the transcription factor NF-kappaB. Blood. 2003;102:662–71.. doi: 10.1182/blood-2002-09-2785. - DOI - PubMed

[6] El Bekay R, Alvarez M, Monteseirin J, Alba G, Chacon P, Vega A, et al. Oxidative stress is a critical mediator of the angiotensin II signal in human neutrophils: involvement of mitogen-activated protein kinase, calcineurin, and the transcription factor NF-kappaB. Blood. 2003;102:662–71.. doi: 10.1182/blood-2002-09-2785. - DOI - PubMed

[7] Garrido AM, Griendling KK. NADPH oxidases and angiotensin II receptor signaling. Mol Cell Endocrinol. 2009;302:148–58.. doi: 10.1016/j.mce.2008.11.003. - DOI - PMC - PubMed

[8] Garrido AM, Griendling KK. NADPH oxidases and angiotensin II receptor signaling. Mol Cell Endocrinol. 2009;302:148–58.. doi: 10.1016/j.mce.2008.11.003. - DOI - PMC - PubMed

[9] Silva-Filho JL, Souza MC, Henriques M, Morrot A, Savino W, Nunes MP, et al. AT1 receptor-mediated angiotensin II activation and chemotaxis of T lymphocytes. Mol Immunol. 2011;48:1835–43.. doi: 10.1016/j.molimm.2011.05.008. - DOI - PubMed

[10] Silva-Filho JL, Souza MC, Henriques M, Morrot A, Savino W, Nunes MP, et al. AT1 receptor-mediated angiotensin II activation and chemotaxis of T lymphocytes. Mol Immunol. 2011;48:1835–43.. doi: 10.1016/j.molimm.2011.05.008. - DOI - PubMed

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A historical perspective on ACE2 in the COVID-19 era

Affiliations

A historical perspective on ACE2 in the COVID-19 era

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